Cystic fibrosis (CF) is a complex, systemic and lethal disorder, involving impaired airway function, endocrine and metabolic disruption, immune dysfunction, and many other traits. The CF mouse recapitulates most of the disease features of the human disorder, including an altered inflammatory profile from infection, endocrine disruption, metabolic anomalies, delayed puberty and infertility, intestinal obstruction, intestinal and airway goblet cell hyperplasia, altered epithelial bioelectric properties, etc., and thus provides numerous phenotypes relevant to the human disease, but consequently requires special husbandry. As a consequence, our local CF Animal Core has become an international distributor of CF and CF-related mice, a training facility for procedures and a resource for assays and mouse tissue samples. Our assortment of CF-related mice continues to grow, as does demand, and here we propose to expand the scope of animals in our colony and to make them available for our own research programs as well as to any investigators requesting them. Additionally, we propose to provide a tissue bank of CF mouse organs and tissues, along with age and sex-matched controls, available to investigators upon request. Lastly, we also propose to carry out transcriptomic and proteomic analyses on matched tissues from CF and non-CF mice and to make these data available to investigators for hypothesis generation and/or testing. The proposal capitalizes on our history with CF mice and an economy of scale not possible for smaller colonies. The CF Animal Core from which this proposal evolved was designed over a decade ago to generate CF animals for investigators at our CF Center, but has evolved well beyond that, providing CF mice, double transgenics, and most recently conditional alleles that we have generated, to investigators around the world. Demand continues to increase, and thus we propose here to provide additional resources that accommodate our own needs as well as those of others pursuing questions related to CF. To accomplish these goals, the specific aims are: 1) to produce murine models of CF disease modifiers to study modifier mechanisms in vivo, 2) to create CF mouse models expressing human CFTR and its disease- causing mutants for studies of CFTR correction or other CFTR studies requiring in vivo contexts, 3) to provide a bank of CF and control mouse organs collected under uniform conditions (age, sex, diet, etc.) and 4) to generate transcriptome and proteome databases from CF mouse tissues for hypothesis generation. PUBLIC HEALTH RELEVANCE (provided by applicant): Animal models are crucial for understanding mechanisms of human disease as well as for developing and testing potential therapies. The project outlined in this application accelerates the availability of cystic fibrosis mouse models, their tissues, mRNA expression and protein expression profiles to investigators interested in CF-related questions.